Chemistry of Immunoglobulins

Ig class IgM structure

1. 10 Ag binding sites --> highest avidity 2. monomer on surface of mature B cell

Ab structure

1. 2 identical heavy chains 2. 2 identical light chains 3. heavy chains joined by disulfide bonds in the hinge region 4. light chains joined to heavy chains by disulfide bonds in Cl region 5. 5 classes of heavy chains include IgG, IgM, IgA, IgE, and IgD 6. 2 types of light chain (k or l) 7*. both heavy and light chains have interchain disulfide bonds 8*. Ab binds Ag at the N-terminal end (Fab)

effector functions of IgE

1. Binds to basophils and mast cells. Causes degranulation --> allergic reaction. 2. has lowest concentration in serum 3. short half-life, but long when on surface of mast cell 4. Protection against worms by causing inflammatory reaction

effector functions of IgM

1. Heaviest isotype 2. appears first during primary immune response 3. best at C' activation 4. best agglutinating Ab

effector functions of IgD

1. Monomer 2. second receptor on B cell after IgM 3. UKNOWN FUNCTION

effector functions of IgG

1. Most prevalent isotype in human serum (blood and lymph) 2. longest half life 3. appears in late primary and early secondary response can activate C' 4. opsonin and mediates ADCC (antigen dependent cellular cytotoxicity)

effector functions of Ig A

1. monomer on B cell surface, dimer when secreted 2. secretory antibody has protective protein (secretory component). The component is added by epithelial cells once the secreted IgA has bound to a poly-Ig receptor on the submucosal side of an epithelial cell. Added so it can be protected in harsh environments. 3. highest concentration in body of all isotypes

Ig class IgG structure

1.Always a monomer 2. 2 Ag binding sites

Ig domain

Ab molecule is made of Ig domains, each about 100-110 amino acids long. Each contains an intrachain disulfide bond. Fold is important in making it apart of the Ig gene superfamily.

Allotype

Allelic forms of same protein that can vary within a species. Usually 1-2 a.a changes

F_c

Area of antibody with biological activity. Comprises total C region. Note: IgG and IgA have subclasses due to minor amino acid difference in the C region.

Fab

Area of the antibody which binds the antigen. Comprised of variable light and heavy chain regions plus C_H1 and C_L regions). Note: Ab will have only one of the two possible light chain types.

framework region

Areas of less variability. They simply provide a framework for the hypervariability region to do the business.

C

C = constant.

What is the biologically active part of an antibody?

Fc (C' activation, ADCC)

What is an immunoglobulin?

Ig = antibody = Ab = gamma globulins. They are synonymous! Ig is a generic term. Ab specifies an Ig with particular specificity.

Which isotypes can be transported via mucus?

IgA and IgM

Which isotypes can induce mast-cell degranulation?

IgE

Which isotypes are able to activate the classical compliment pathway?

IgG and IgM

Which isotypes are present on the membrane of mature B cells?

IgM and IgD

Significance of multiple myeloma

Isolation of monoclonal Abs from myeloma patients allowed for characterization of generic Ig structure

hypervariable region

Regions that determine complementarity to the antigen. Concentrated in three regions called CDR (complement determining regions) including CDR1, CDR2, CDR3. Usually exposed so they can more easily contact the antigen. CDR3 is most important in contacting antigen.

Ag specificity

The Ag specificity of B cells is because of their membrane bound Ig. A single Ab can only bind to ONE antigen. After the initial binding of the Ag to a membrane bound Ig, the B cell is activated and can develop a plasma cell. The plasma cell secretes soluble Abs specific to ONE antigen. Specificity possible because of clonal selection and proliferation.

Isotype

These are the 5 classes of heavy chains. Determined by C (constant)-regions of H-chains

V_h

Variable part of the heavy chain

Do the membrane and secreted forms of Ab differ?

Yes. IgG, IgD, and IgE stay as monomer. IgA becomes a dimer joined by a j chain. IgM becomes a pentamer joined by a j-chain and multiple disulfide bonds.

C_H

constant part of the heavy chain

Idiotype

due to the variable region (e.g. CDRs) of the Ig (differences in a.a. sequences due to variable binding to Ags) essentially a clonal marker for a given B cell

Significance of Bence-Jones proteins

light chains released into urine. Helped characterize generic Ig structure.

Which isotypes can cross the placenta?

some subclasses of IgG

V_l

variable part of the light chain